The mechanisms responsible for the production of experimental allergic encephalomyelitis (EAE), a model of autoimmune disease which is manifested by demyelination, are being examined. The studies are being conducted in mice because this species is ideally suited for the analysis of immunologic and genetic factors related to disease. Three forms of the murine disease have been produced: 1) Acute EAE, 2) Chronic Relapsing EAE and 3) Adoptively Transferred EAE. Current research is focused on the adoptively transferred model. The transfer of lymphocytes sensitized aginst myelin basic protein leads to neurological dysfunction characterized pathologically by inflammation and primary demyelination. Many mice recover and develop chronic relapsing disease. The mechanisms responsible for both the initial and the chronic disease are not known, but an early event is the migration of immune cells across the blood-brain barrier into the central nervous sysem (CNS). The subpopulation of T-lymphocytes which is responsible for the disease are Ly1+ 2- and react with antigen in association with class II MHC (Ia) molecules. Immunohistochemical examination of CNS endothelial cells in tissue section and the cytofluorographic studies of whole cells freshly isolated from the CNS indicate class II MHC molecules are not expressed on normal endothelial cells but appear during the development of EAE. Immune lymph node cells with the capacity to transfer EAE produce gamma interferon which can induce the expression of Ia molecules on endothelial cells. These observations have led to the hypothesis that interaction between immune cells and the capillary endothelium leads to alterations of the blood-brain barrier.